For various reasons, e.g., vessel wall narrowing caused by various diseases, it sometimes becomes necessary to treat the lumen of vessels or cavities which carry body fluids, for example, blood vessels. The present invention is directed to the prophylaxis of problems which may occur as a result of such treatments and diseases.
For example, treatment may be necessary to cure the effects of arteriosclerosis, a degenerative disease in which atheromatous plaques cause the stenosis, or narrowing, of a human blood vessel such as an artery or vein. Atheromatous plaques may comprise, for example, any of the following, including combinations thereof: lipids or other fatty matter, fibrous materials, calcium, blood cells, collagen or other thrombotic deposits. An area of atheromatous plaque located on an artery wall is known as a "lesion".
Briefly, atheromatous plaque, which has the ability to ultimately result in the formation of a lesion, may begin developing by the accumulation of lipid-laden cells in the intimal layer of the artery wall. Examples of lipid-laden cells which are found in the circulating blood include monocytes and macrophages. An accumulation of such lipid-laden cells in the intimal layer of the artery wall may become likely when lipid-laden cells adhere to the endothelial layer of the artery wall. Once the lipid-laden cells or lipid vesicles are present in the endothelial layer, lipids are highly susceptible to passing through the endothelial cells to the intima. A lesion may be formed upon further continuation of this process.
In instances when stenosis caused by atheromatous plaque reduces blood flow through an artery, the tissue or organ distal to the stenosis fails to receive an adequate blood supply, thereby severely compromising such tissue or organ. An acute lapse in the blood supply to the brain (a stroke) or heart (a heart attack) can be fatal or cause severe tissue damage. Further, other disfunctions of organ physiology can be caused by chronic processes which are related to stenotic lesions. As a result, special procedures have been developed to combat stenosis of commonly affected arteries such as the aorta, iliac, femoral, coronary and cerebral arteries.
Although bypass surgery, such as coronary artery bypass surgery, is often used to repair damaged and blocked portions of arteries, percutaneous transluminal angioplasty ("PTA") and percutaneous transluminal coronary angioplasty ("PTCA") have been developed as an alternative to bypass surgery in order to repair blocked or partially blocked arteries. Since the introduction of PTA and PTCA, also known as "balloon angioplasty," these techniques have been performed in millions of patients for the treatment of arterial stenosis.
Certain other procedures have also been developed to repair blocked or partially blocked arteries. An example of such a further procedure is atherectomy, in which a rotating blade located on the distal tip of a catheter is placed at the site of a lesion. The rotating blade serves to reduce the size of the lesion by shearing plaque off the arterial wall. Another procedure developed to repair blocked or partially blocked body vessels (e.g., arteries) uses a laser-equipped catheter, in which a laser located on the distal tip of a catheter is placed at or near the site of a lesion. The laser serves to reduce the size of the lesion by shearing plaque off the arterial wall. Stent implantation and slurry treatments are further examples of recently developed procedures for the treatment of blocked arteries.
In many instances, however, treatment of the body vessel or cavity by one of the above-described procedures is not entirely satisfactory because the surgical procedure may damage, traumatize or incompletely treat the vessel or cavity. In relation to blood vessels, due to various factors, some of which are incompletely understood, clinically relevant restenosis (the reappearance of stenosis) has been found to occur in up to 50% of patients who had received PTA and PTCA treatments.
Restenosis may occur, for example, as a result of the damage and trauma caused to vessel walls by the high balloon pressure which is used in PTA and PTCA procedures. For example, when trauma denudes the vessel wall of endothelial cells, exposing the inner layers of cells to flowing blood, various mechanisms (e.g., repair mechanisms such as smooth muscle cell proliferation and migration) may lead to restenosis of the vessel. Therefore, one goal of a treatment for preventing restenosis of a blood vessel is to prevent exposure of the inner tissue layers of the artery wall to blood. As a general matter, it will usually be desirable to prevent the exposure of the inner layers of any afflicted (e.g., diseased) portion of a body vessel or cavity to the body fluid which is found therein.
Restenosis may also result from the portion of plaque which will generally remain on the artery wall even after a procedure such as balloon angioplasty has been performed on a lesion. Endothelial cells cover the surface of blood vessels and render the surface non-thrombogenic and non-reactive. Where plaque remains on the artery wall, this portion of the artery wall lacks the protection provided by the endothelial cells. Therefore, further plaque is likely to build up on the plaque which remains after the angioplasty procedure.
A still further cause of restenosis is that, as a result of the body's immune response, white blood cells may attach themselves to any plaque or damaged arterial wall which persists after one of the above-described procedures has been performed. After these white blood cells attach to this area, further plaque may easily build up.
The danger of restenosis generally also exists after the use of the non-balloon procedures (atherectomy and laser-equipped catheters) mentioned above. These procedures have several disadvantages, including the danger that if the laser or the cutting blade is not properly oriented in use, damage to the vessel wall may result. Such damage may have a high probability of leading to restenosis for the reasons described above.
Stent implantation (such as that described in U.S. Pat. No. 5,100,429 to Sinofsky et al.), which shields a lesion and provides structural support, is generally undesirable because the procedure will narrow the vessel opening at the stent location and introduce a foreign body into the vessel which itself is likely to promote stenosis. Foreign bodies are both subject to (a) attack by white blood cells, leading to the dangers discussed above, and (b) promoting the formation of a thrombus. Thrombotic particles are likely to build up at the endpoints of the stent.
Therefore, any treatment of the vessel which has the possibility of damaging or causing trauma to the vessel, including surgery, PTA, PTCA, atherectomy, laser and slurry treatments, may lead to restenosis.
Accordingly, where a body vessel or cavity has been treated to relieve a disorder such as a blockage, it is desirable to have the ability to further treat that site to overcome the problems discussed above. For example, it is desirable to further treat the site of an angioplasty procedure in order to prevent restenosis of the artery.
It is also desirable that, during such further treatment, blood or other body fluid be supplied to the distal side of the site of treatment, e.g., so that downstream tissues are not deprived of oxygen and other nutrients supplied by the blood. This will also enable the body to carry on its normal functions during the procedure.
It is also desirable that such further treatment include the ability to isolate the treatment site from the flow of the body fluid (e.g., blood). In this manner, the site may be treated without interference by the body fluid. Where the treatment site is isolated it is also desirable to have the ability (a) to rinse and flush the isolated site to prepare the vessel or cavity walls (e.g., arterial walls) for this further treatment, (b) to dispense medication and (c) to protect the vessel or cavity wall, for example, from mediators which may cause restenosis after PTA, PTCA or atherectomy.